Biological Activity Profiles of 1α, 25-Dihydroxyvitamin D_2,D_3,D_4,D_7,and 24-Epi-1α, 25-dihydroxyvitamin D_2

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概要

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• We have synthesized several 1α, 25-dihydroxyvitamin D [1α, 25(OH)_2D] derivatives and evaluated their biological activity in terms of their binding affinity for the vitamin D receptor (VDR) and vitamin D-binding protein(DBP), antiproliferative ro differentiation-inducing effects on human promyelocytic leukemic HL-60 cells, and transcriptional activity on a rat 25-hydroxyvitamin D_3-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), and human osteocalcin gene promoter, including a VDRE in transfected human osteosarcoma MG-63 cells. Furthermore, human VDR- or retinoic acid X receptor α (RXRα)-mediated luciferase activities of the derivatives were also measured by a one-hybrid system in human epitheloid carcinoma, cervix HeLa cells and African green monkey kidney CV-1 cells. Binding affinity for VDR, bone-resorbing activity, antiproliferative and cell-differentiating effects, transactivation potencies on target genes and VDR- or RXRα-mediated gene regulations of 1α, 25(OH)_2D_2 and 1α, 25(OH)_2D_4 were almost comparable to the effects of 1α, 25(OH)_2D_3 while 24-epi-1α, 25(OH)_2D_2 and 1α, 25(OH)_2D_7 were much less active than 1α, 25(OH)_2D_3 in these respects. This is the first report concerning biological assessment of 1α, 25(OH)_2D_2,1α, 25(OH)_2D_3,1α, 25(OH)_2D_4,24-epi-1α, 25(OH)_2D_2 and 1α, 25(OH)_2D_7 at the molecular level, especially with regards to the structural differences at the 24R- or 24S-methyl group and a double bond between carbons 22 and 23 in the side chain of 1α, 25(OH)_2D derivatives.

• 公益社団法人日本薬学会の論文
• 1999-04-15

著者

• NAKAGAWA Kimie

  Department of Hygienic Science, Kobe Pharmaceutical University

• Okano Toshio

  Department Of Hygienic Science Kobe Pharmaceutical University

• 津川 尚子

  神戸薬大

• Kawamoto Yuko

  Department Of Hygienic Science Kobe Phamaceutical University

• Tsugawa Naoko

  Department Of Hygienic Sciences Kobe Pharmaceutical University

• Hayashi Toshiya

  Fine Chemical Research Laboratory Nisshin Flour Milling Co. Ltd.

• TACHIBANA Yoji

  Fine Chemical Research Laboratory, Nisshin Flour Milling Co., Ltd.

• OZONO Keiichi

  Environmental Medicine, Research Institute, Osaka Medical Center for Maternal and Child Health

• Tachibana Yoji

  Fine Chemical Research Laboratory Nisshin Flour Milling Co. Ltd.

• Kawamoto Yuko

  Department of Clinical Neurology and Stroke Medicine, Yokohama City University, Japan

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